Serotonin (5-HT) receptors are known to have a plurality of subtypes such as 5-HT1, 5-HT2, 5-HT3 and 5-HT4. These 5-HT4 receptors are disclosed in, for example, European Journal of Pharmacology 146 (1988), 187–188, and Naunyn-Schmiedeberg's Arch. Pharmacol. (1989) 340:403–410.
5-HT4 receptor modulators (e.g., agonists and antagonists) are found to be useful for the treatment of a variety of diseases such as gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, irritable bowel syndrome, constipation, dyspepsia, esophagitis, gastroesophageral disease, nausea, central nervous system disease, alzheimers disease, cognitive disorder, emesis, migraine, neurological disease, pain, and cardiovascular disorders such as cardiac failure and heart arryhthmia (See TiPs, 1992, 13, 141; Ford A. P. D. W. et al., Med. Res. Rev., 1993, 13, 633; Gullikson G. W. et al., Drug Dev. Res., 1992, 26, 405; Richard M. Eglen et al, TiPS, 1995, 16, 391; Bockaert J. Et al., CNS Drugs, 1, 6; Romanelli M. N. et al., Arzheim Forsch./Drug Res., 1993, 43, 913; Kaumann A. et al., Naunyn-Schmiedeberg's. 1991, 344, 150; and Romanelli M. N. et al., Arzheim Forsch./Drug Res., 1993, 43, 913).
A variety of oxy-pyridine compounds have been known as 5HT receptor antagonists or agonists. WO 94/07859 discloses oxy-pyridine compounds as 5HT4 antagonists. WO93/08185; Japanese Patent Publication Laid-Open No. H09-067,347 and H10-203,987; describe a variety of oxy-pyridine compounds as 5HT3 receptor antagonists.
Also, oxy-pyridine compounds synthesized for different uses are described in WO96/31475; WO01/5763; WO 99/50247; WO 97/27852; WO91/00858 and EP 274867.
It would be desirable if there were provided 5HT4 receptor modulators (e.g., agonists and antagonists) which have more 5HT4 receptor modulating activities (e.g., angonist or antagonist activities).